At least that seems to be the message in a recent study of humble roundworms that helps solve the mystery behind the only scientifically-verified way for creatures to live longer — calorie restriction.

Since the 1930s, when researchers at Cornell University in Ithaca, N.Y., showed that rats on a low-calorie diet live twice as long as their normal-diet brethren, scientists have explored life extension through caloric restriction. Studies have shown that eating perhaps 70% of the calories normally consumed, while also eating adequate vitamins and other nutrients, extends the life of everything from simple yeasts to mice by about 40%.

Since people live so much longer by comparison, testing the idea on humans hasn't yet proven a definite link to longer life. Researchers at Washington University in St. Louis reported last year that volunteers in one longevity-diet study had cardiovascular systems that were much healthier than normal, with 55-year-old study participants reporting blood pressure readings more typical of 20-year-olds. Study volunteers ate as little as 1,400 calories a day, rather than the 2,000 or more calories in a typical adult's diet.

But the reason why this all works, whether through improved immune systems, less heart disease or better-working hormones, has eluded researchers. In a recent Nature study, Nicholas Bishop and Leonard Guarente of Massachusetts Institute of Technology in Cambridge fill in a piece of the puzzle, reporting the discovery of a brain center in roundworms that seems to be the wizard behind the curtain. Caloric restriction's benefits may be all in your head, they argue, not your guts.

A lot of genes have been implicated in caloric restriction's longevity effects, but in the roundworms, the researchers found that a gene called skn-1b seems essential. People have forms of this gene, which is thought to play a role in skin formation early in life and acts as an antioxidant, removing damaging chemicals from the bloodstream later in life. In the roundworms, the gene seems only expressed in the brain (as much of a brain as roundworms possess) from two neuron, or brain cells, called the ASI.

"To confirm that the ASI neurons are required for diet-restriction-induced longevity, we used a laser microbeam to specifically kill these two cells and tested the effect in subsequent dietary restriction," report Bishop and Guarente. Destruction of these neurons "completely suppressed the response to dietary restriction," they conclude, meaning that fewer calories no longer meant longer life. To double-check, they inserted a gene that turns fluorescent into a fresh batch of roundworms. That fluorescent gene was designed to light up when the skn-1b gene was turned on. And as expected, the researchers saw the neurons glow brightly when the worms were subjected to caloric restriction and received the longevity benefit.

So there you have it, a brain center that seems to control longevity.

"It's an intriguing study. It will lead to a whole lot more experiments," says biochemist Brian Kennedy of the University of Washington in Seattle. The key news is the suggestion that it's not just the amount of food but the brain's awareness of food intake that is responsible for the effects of calorie restriction. "That's a new way to think about calorie restriction," Kennedy says.

To figure out how these neurons were doing their work, the study authors next researched the "whole-body respiration rate" of roundworms on a calorie-restricted diet and found that the roundworms take in more oxygen, as well as release antioxidant-related genes in their guts. At least 15 hormones, including the insulin released in response to eating, are released in cascades by the skn gene, and the hormone signal from this activity may be what extends the life of the roundworms.

A related study in the same edition of Nature, led by Andrew Dillin of the Salk Institute for Biological Studies in La Jolla, Calif., finds that a compound called PH-4, which acts to quiet or increase gene activity, also seems to play a role in releasing the benefits of caloric restriction in roundworms.

So, good news for roundworms. But what about us mammals? Well, researchers including Guarente (who, like a lot of longevity researchers is a founder and stockholder in a firm looking to someday sell longevity treatments), have found that the genes involved in caloric restriction are highly "conserved." Conserved genes turn up in slightly altered forms in animals ranging from primitive creatures, like yeasts, to complex ones, like mammals. Researchers suppose that from an evolutionary standpoint, longevity from caloric restriction, which extends the breeding life but lowers the fertility of creatures, may have allowed animals to survive periods of famine. That is a pretty useful trick and for that reason, the genes remain in the genomes of creatures over the long haul.

For us pill-popping humans, the final goal is the creation of a drug over the next few decades that somehow mimics the hormonal cascade that triggers longevity or else fools a mammalian brain center into facilitating longevity. "We anticipate that future work will dissect the critical central hormones mediating diet-restriction-induced longevity of worms and mammals," the study concludes. At least we better hope so, if we want to avoid a 1,400 calorie diet.

"I wouldn't say it is time for people to get excited about a magic pill," cautions Kennedy. "But (this kind of research) is the only way we are going to find out how calorie restriction works."

Each week, USA TODAY's Dan Vergano combs scholarly journals to present the Science Snapshot, a brief summary of some of the latest findings in scientific research. For past articles, visit this index page.

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A fluorescent microsocopic view of the muscles of C. elegans, humble roundworms that may help solve the mystery behind the only scientifically-verified way for creatures to live longer — calorie restriction.

The simple structure of Caenorhabditis elegans, more commonly known as the roundworm.

By Cori Bargmann, UCSF

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